Delgocitinib-JTE-052-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDelgocitinibCat. No.: HY-109053CAS No.: 1263774-59-9Synonyms: JTE-052分式: CHNO分量: 310.35作靶點(diǎn): JAK作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DM

2、SO : 58 mg/mL (186.89 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.2222 mL 16.1108 mL 32.2217 mL5 mM 0.6444 mL 3.2222 mL 6.4443 mL10 mM 0.3222 mL 1.6111 mL 3.2222 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Delgocitinib種新型且有

3、特異性的 JAK 抑制劑, 對 JAK1, JAK2, JAK3 和 Tyk2 的 IC50 值分別為 2.8, 2.6, 13和 58 nM。IC50 & Target JAK2 JAK1 JAK3 Tyk22.6 nM (IC50) 2.8 nM (IC50) 13 nM (IC50) 58 nM (IC50)1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 In the enzymatic assays, Delgocitinib potently inhibits all of the JAK subtypes with IC5

4、0 values of 2.80.6,2.60.2, 130 and 589 nM for JAK1, JAK2, JAK3 and Tyk2, respectively. Lineweaver-Burk plots show thatthe inhibition mode of Delgocitinib toward all JAKs is competitive with ATP with Ki values of 2.10.3, 1.70.0,5.50.3 and 141 nM for JAK1, JAK2, JAK3 and Tyk2, respectively. In these c

5、ell-based cytokine signalingassays, Delgocitinib inhibits the phosphorylation of Stat proteins induced by IL-2, IL-6, IL-23, GM-CSF, andIFN- with IC50 values of 409, 3314, 8411, 30422 and 183 nM, respectively. Delgocitinib also inhibitsIL-2-induced proliferation of T cells in a concentration-depende

6、nt manner (IC50=8.93.6 nM), and its potencyis similar to that of tofacitinib (IC50=16 nM) 1.體內(nèi)研究 Delgocitinib decreases the IFN- production, but the potency of the 1-h prior administration is higher than thatof the 6-h prior administration (ED50=0.24 versus 1.3 mg/kg). In the administration from day

7、 1, Delgocitinibprevents the development of hind paw swelling and histological changes of inflammatory cell infiltration andsynovial cell hyperplasia. Delgocitinib inhibits radiographic and histological changes of bone destruction andcartilage destruction. In the administration from day 15, Delgocit

8、inib decreases the paw swelling in a dose-dependent manner. In addition, Delgocitinib ameliorates the inflammatory cell infiltration, synovial cellhyperplasia, and cartilage/bone destructions in the histological and radiographic examinations at the end ofthe study 1.PROTOCOLCell Assay 1 For determin

9、ation of IL-2-induced T cell proliferation, human T cells are precultured with 10 g/mL PHA-M for3 days and plated in 96-well plates at 1.0104 cells/well in the presence or absence of variousconcentrations of Delgocitinib. Following preincubation with Delgocitinib for 30 min at 37C, the cells arestim

10、ulated by adding 20 ng/mL recombinant human IL-2 to each well and incubated for 3 days at 37C under5 % CO2. After completion of the culture period, the cells are harvested with a 96-well harvester and countedin a scintillation counter 1.MCE has not independently confirmed the accuracy of these metho

11、ds. They are for reference only.Animal Lewis rats are used in this study. First, collagen-induced arthritis (CIA) is induced in rats. Lewis rats areAdministration 1 immunized with 1 mL of the emulsion (1 mg of type II collagen) via ten intradermal injections on the backunder anesthesia. The rats are

12、 then challenged with 0.2 mL of the emulsion injected into the base of the tailon day 8 under anesthesia. Delgocitinib is given orally once daily from day 1 to day 21 (preventiveadministration) or from day 15 to day 28 (therapeutic administration). After arthritis induction, the hind pawvolume is me

13、asured by a water displacement method using a plethysmometer. On day 22 or day 29, the ratsare euthanized, and their hind paws are excised and X-rayed or processed for histological evaluation 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Tanimoto A, et al. Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responsesin vitro and in vivo. Inflamm Res. 2015 Jan;64(1):41-51.McePdfHeight2/2 Master of Small Molecules 您邊